Giraffe Or Leopard Spot Chorioretinopathy As an Outstanding Finding: Case Report and Literature Review

Int Ophthalmol (2019) 39:1405–1412 https://doi.org/10.1007/s10792-018-0948-5

CASE REPORT

Giraffe or leopard spot chorioretinopathy as an outstanding ﬁnding: case report and literature review

Mohammad Hossein Jabbarpoor Bonyadi . Vahid Ownagh . Ehsan Rahimy . Masoud Soheilian

Received: 11 April 2017 / Accepted: 3 June 2018 / Published online: 8 June 2018 Ó Springer Nature B.V. 2018

Abstract 2-year follow-up, she underwent cataract surgery and Purpose Presentation of two typical cases with later on developed neovascular glaucoma in her both characteristic leopard retinopathy secondary to bilat- eyes. The second case was a 45-year-old man who had eral diffuse uveal melanocytic proliferation (BDUMP) developed decreased visual acuity in his left eye for and idiopathic uveal effusion syndrome (IUES) and 3 years. Anterior segment examination was unremark- brief review of the literature about leopard spot able, and both eyes had normal intraocular pressure. retinopathy. No vitreous inflammation was observed. Fundoscopy Case report A 43-year-old women, who was a revealed diffuse exudative retinal detachment in his known case of ovarian carcinoma, referred with left eye. Fluorescein angiography showed leopard spot gradual bilateral visual loss. In ophthalmic examina- retinopathy of posterior pole, and EDI-OCT disclosed tion, subretinal fluid, multiple patchy subretinal subfoveal choroidal thickening. After exclusion of hyperpigmented lesions and leopard spot chori- other causes of exudative retinal detachment and with oretinopathy were evident in her both eyes. Fluores- diagnosis of IUES, he underwent intravitreal triamci- cein angiography showed multiple nummular nolone injection (2 mg) which improved his final hyperfluorescent lesions surrounded by zones of vision to 20/40. hypofluorescence. Spectral domain optical coherence Conclusion Leopard spot retinopathy is an uncom- tomography revealed increased retinal thickness, mon but clinically distinct manifestation of various subretinal fluid and RPE irregularities in both eyes. disorders. BDUMP may present with leopard spot Enhanced depth imaging OCT (EDI-OCT) showed retinopathy, anterior uveal tract involvement and bilateral subfoveal choroidal thickening. During next neovascular glaucoma. As EDI-OCT showed involvement and increased thickening of choroid in both cases of BDUMP and IUES, it may be better to consider such cases as leopard chorioretinopathy and catego- rize these entities as a member of pachychoroid M. H. Jabbarpoor Bonyadi Á V. Ownagh Á pigment retinopathy disorders. M. Soheilian (&) Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, No. 23, Paidarfard St., Pasdaran Keywords Bilateral diffuse uveal melanocytic Ave., Tehran 16666, Iran proliferation (BDUMP) Á Idiopathic uveal effusion e-mail: [email protected] syndrome (IUES) Á Leopard retinopathy Á Giraffe E. Rahimy retinopathy Á Optical coherence tomography (OCT) Palo Alto Medical Foundation, Palo Alto, CA, USA 123 1406 Int Ophthalmol (2019) 39:1405–1412

Fig. 1 For BDUMP case, fundus photographs demonstrate pigmented leopard pattern lesions. Fundus autofluorescence imaging shows patchy areas of hypoautofluorescence surrounded by zones of increased autofluorescence in a leopard spot pattern

Introduction Leopard pattern of the fundus is a characteristic finding in BDUMP [4, 5]. Rarely iris involvement in Leopard (also called Giraffe) spot retinopathy is a the form of multiple pigmented and nonpigmented characteristic fundoscopic and angiographic finding placoid nodules has also been reported in this which may be caused by heterogeneous group of syndrome [6]. disorders. Our second case which caused unilateral leopard Bilateral diffuse uveal melanocytic proliferation retinopathy was a middle-age man with diagnosis of (BDUMP) and idiopathic uveal effusion syndrome chronic IUES. This case also showed dramatic (IUES) are among disorders which are causes of responses with intravitreal triamcinolone injection. leopard spot retinopathy. IUES also may be associated with leopard retinopathy BDUMP is a rare paraneoplastic disease accompa- [7]. nied by painless bilateral visual loss. It is characterized Herein, we report a rare case of BDUMP with by multiple round-to-oval orange patches at the level characteristic leopard fundus pattern which was also of the retinal pigment epithelium (RPE), multifocal associated with iris stromal involvement, rubeosis early hyperfluorescence corresponding to these iridis and neovascular glaucoma. Interestingly, we patches, diffuse thickening of the uveal tract with observed mild reduction of exudative retinal detach- focal nodules, exudative retinal detachment and ment in this case with injection of intravitreal beva- rapidly progressive cataract [1]. Rarely anterior seg- cizumab. The second case is a middle-age man with ment involvement with iris and ciliary body cysts diagnosis of chronic IUES and typical unilateral formation, glaucoma, dilated episcleral vessel and leopard spot retinopathy which improved with intrav- shallow anterior chamber has been reported [2, 3]. itreal triamcinolone injection. We report our enhanced

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Fig. 2 For BDUMP case: fluorescein angiography (FAG) shows leopard pattern of multiple nummular hyperfluorescent lesions surrounded by zones of hypofluorescence (inverse FAF pattern). ICG (lower images) demonstrates leopard pattern hypercyanescent spots (inverse FAF pattern)

depth imaging (EDI) OCT findings of choroidal chemotherapy with paclitaxel and carboplatin thickening in the above-mentioned cases, and we also regimen. report a brief review of the literature for other several At her initial visit to us, visual acuity was 3/10 in causes of leopard retinopathy. the right and 2/10 in the left eye. Slit-lamp examination of anterior segment was unremarkable, and there was no flare/cell in anterior chamber or vitreous Case report cavity. Dilated fundoscopic examination revealed multiple patchy subretinal hyperpigmented lesions. CASE 1: A 43-year-old woman was referred to our These lesions were round/oval shaped with discrete clinic complaining gradual visual blurring in both borders distributed mostly in posterior pole with eyes. Six months prior visiting us, she had undergone extension to equatorial area mimicking leopard spot electroretinogram (ERG), electro-oculogram (EOG), pattern (Fig. 1). On fundus autofluorescence (Heidel- indocyanine green angiography (ICG) and fundus berg Engineering, Inc., Heidelberg, Germany), the fluorescein angiography (FFA) for mild blurring of lesions in the posterior pole were hypoautofluorescent vision which were reported within normal limit. One (Fig. 1). Fluorescein angiography (Heidelberg Engi- year earlier, this lady had history of total hysterectomy neering, Inc., Heidelberg, Germany) revealed leopard and salpingo-oophorectomy for metastatic papillary pattern of multiple nummular hyperfluorescent lesions serous carcinoma of the ovary. Following radical surrounded by zones of hypofluorescence (Fig. 2). surgery, she had also undergone six cycles of These lesions remained hyperfluorescent in the late phase of angiogram without significant leakage.

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Fig. 3 For BDUMP case: SD-OCT shows neurosensory bevacizumab injection, there is resolution of subretinal ﬂuid detachment, RPE irregularities with hyperreﬂective subretinal specially in the left eye (Lower part) depositions and choroidal thickening. Following intravitreal

phases. Spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering, Inc., Heidel- berg, Germany) revealed increased retinal thickness, subretinal fluid with neurosensory detachment and RPE irregularities with hyperreflective subretinal depositions in both eyes (Fig. 3). Imaging of choroid using enhanced depth imaging OCT (EDI-OCT, Spectralis, Heidelberg Engineering, Inc., Heidelberg, Germany) in the subfoveal area showed bilateral choroidal thickening. Ultrasonic biomicroscopy (UBM, ELLEX MEDICAL Inc., Adelaide, Australia) Fig. 4 Hyporeflective ciliary body cystic lesions are evident in revealed multiple hypo-reflective ciliary body thick- ultrasonic biomicroscopy ening and cystic lesions, narrowing of anterior chamber angle and hyperreflective iris lesions (Fig. 4). Indocyanine green angiography (ICG, Heidelberg Visual acuity and fundoscopic findings remained Engineering, Inc., Heidelberg, Germany) also showed unchanged during the first follow-up year. Later on, leopard pattern hypercyanescent spots in early and late she developed mature cataract in the left eye and

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Fig. 5 Slit-lamp photography shows hyperpigmented iris lesion

underwent cataract extraction with posterior chamber eye for 3 years without any positive past systemic IOL implantation. During the second-year follow-up, history. His best visual acuity was 20/20 in the right she demonstrated local recurrence of carcinoma and and finger counting at 3 meters in the left eye. Anterior underwent three additional cycles of the mentioned segment examination was unremarkable, and both chemotherapy regimen and at this time the visual eyes had normal intraocular pressure without any acuity gradually decreased (to finger counting 2–3 m medication. On slit-lamp examination, no vitreal cell in both eyes); OCT also revealed increased macular was observed. Fundoscopy revealed exudative retinal thickness with bilateral subretinal fluid again. There- detachment with diffuse shifting fluid involving fore, she underwent intravitreal injection of Beva- inferior retina and posterior pole in his left eye. cizumab (Avastin 1.25 mg, Genentech, South San Subretinal fluid was evident on spectral domain OCT, Francisco, California USA) in her both eyes for and EDI-OCT showed subfoveal choroidal thickening possible treatment and fortunately her left eye macular (Fig. 6). Following one internist consult and after thickness responded and improved (Fig. 3). exclusion of other inflammatory/noninflammatory At the final visit, a grayish lesion was observed in causes of exudative retinal detachment [7] and with her iris stroma of left eye with development of rubeosis a most possible diagnosis of idiopathic uveal effusion iridis and neovascular glaucoma in both eyes (Fig. 5). syndrome (IUES), he underwent intravitreal triamci- Unfortunately she passed away shortly after this last nolone 2 mg (Triamcinolone acetonide, TriamHexal, visit because of systemic condition deterioration. 2 mg/0.05 ml, Holzkirchen, Upper Bavaria, Ger- many) injection which caused incredible improvement in his vision to 20/40 after 2 weeks. Following Case 2 treatment subretinal fluid absorbed completely with residual subretinal fibrotic band. At this time, fluores- A 45-year-old man was referred to our clinic with cein angiography showed leopard spot retinopathy of long-term period of decreased visual acuity in his left posterior pole (Fig. 7). His vision (with no refractive

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Fig. 6 In our IUES case, OCT shows neurosensory detachment and RPE irregularities in the left eye (upper image). Following intravitreal triamcinolone injection OCT demonstrates resolution of subretinal ﬂuid, formation of subretinal ﬁbrotic tissue and choroidal thickening (lower image)

error in both eyes) was stable up to his last follow-up spots in hypertensive choroidopathy can also manifest visit at 1 year later. as leopard pattern choroidopathy [23]. Most reported cases of BDUMP in the literature are associated with involvement of posterior uvea. Glau- Discussion coma, dilated episcleral vessels, iridocyclitis, shallow anterior chamber, ciliary body cysts and iris nodules Several pathologic conditions have been reported have been reported as possible anterior segment which may have caused leopard (giraffe) spot pattern involvement in BDUMP [2, 3, 6]. In this report, we in fundoscopy and/or angiography, including BDUMP presented our BDUMP case following papillary serous [4, 5], uveal effusion syndrome [7], leukemia [8], ovarian carcinoma with characteristic leopard spot chronic central serous chorioretinopathy (CSC) [9], chorioretinopathy and subsequent iris involvement unilateral retinal pigment epithelium dysgenesis with pigmented melanocytic tumor leading to devel- [10–12], infantile Refsum disease [13], organ trans- opment of neovascular glaucoma. plant chorioretinopathy [14], beta-thalassemia [15], SD-OCT findings in our patient included RPE systemic argyrosis [16], large-cell lymphoma [17], degeneration and clumping, serous neurosensory recurrent leukemia [18], neonatal adrenoleukodystro- detachment, highly reflective subretinal depositions, phy [19], Walker–Warburg syndrome [20], syphilitic cystic retinal edema and retinoschisis with deposition placoid chorioretinitis [21], psudoxanthoma elasticum of reflective material. Such findings are in close [22], hypertensive choroidopathy [23] and primary accordance with previous report of SD-OCT findings intraocular lymphoma (PIOL) [24]. Regarding hema- in BDUMP cases [26]. tology system, leopard spot pattern has been reported Our patient underwent intravitreal injections of in a variety of such disorders [15, 17, 18, 25]. Elschnig anti-VEGF with transient response of decreased 123 Int Ophthalmol (2019) 39:1405–1412 1411

Fig. 7 In our IUES case, Leopard pattern of ﬂuorescein angiography (left part) visible more than indocyanine green angiography (right part)

subretinal fluid. There are limited reported cases of angiography [7]. Our case was a middle-age man with BDUMP with anterior segment and anterior uveal diagnosis of chronic IUES and typical unilateral tract involvement [2, 3, 6]. One of the unique findings retinal pigment epithelial changes (leopard spot evi- in our case is involvement of anterior uveal by dent on fluorescein angiography images) with reduced pigmented melanocytic lesion on iris surface, iris visual acuity. Although systemic steroids have not neovascularization and neovascular glaucoma. While appeared to be effective in IUES [7], our case this iris finding may be considered as metastatic lesion responded dramatically to intravitreal triamcinolone from underlying ovarian carcinoma, we did not have with visual acuity improvement and complete subreti- histologic access for pathologic confirmation. It has nal fluid absorption. Although this disease has relaps- been proposed that BDUMP may have metastatic ing–remitting clinical course, our case had relatively potential; for example, Duong et al. [27] have already long period of remission with intravitreal triamci- reported a case of BDUMP associated with ovarian nolone injection. After intravitreal treatment, he had carcinoma and metastatic malignant amelanotic mel- no disease relapse during 1 year of follow-up. anoma to the skin. Additionally, there is also a rare Furthermore, because EDI-OCT disclosed choroi- case report of ovarian tumor metastasis to iris similar dal thickening in both of our cases, we believe for to our case [28]. possible change of the term ‘‘leopard retinopthy’’ to Uveal effusion syndrome is another rare disorder ‘‘leopard chorioretinopathy’’ because RPE health has characterized with uveal effusion and serous retinal been postulated to be dependent on healthy choroidal detachment causing secondary changes in RPE. This is circulation, and choroidal abnormality has been shown a classic disease associated with leopard pattern to cause RPE abnormality and dysfunction [29]. In retinopathy in both fundoscopy and fluorescein conclusion, we suggest that leopard spot 123 1412 Int Ophthalmol (2019) 39:1405–1412 chorioretinopathy could be categorized as a group of 14. Abalem MF, Carricondo PC, Pimentel SL, Takahashi WY entities causing pachychoroid pigment retinopathy (2015) Idiopathic organ transplant chorioretinopathy after liver transplantation. Case Rep Ophthalmol Med and RPE involvement is secondary to choroidal 2015:964603 involvement. This categorization needs future accom- 15. Sorcinelli R, Sitzia A, Figus A, Lai ME (1985) Ocular plishment of EDI-OCT or swept source OCT study in findings in beta-thalassemia. Metab Pediatr Syst Ophthal- the other cases of this type of chorioretinopathy. mol 1990(13):23–25 16. 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